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Alport Syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Bloody urine (hematuria) and protein in the urine (proteinuria) are common features of this condition. Alport Syndrome can also affect the eyes causing ocular abnormalities including cataracts, lenticonus, keratoconus, as well as retinal flecks in the macula and mid periphery.
Alport Syndrome is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes, which are involved in collagen biosynthesis. Mutations in any of these genes prevent the proper production or assembly of the type IV collagen alpha3-4-5 network, which is an important structural component of basement membranes in the kidney, inner ear, and eye. Basement membranes are thin, sheet-like structures that separate and support cells in many tissues. When mutations disrupt the formation of type IV collagen fibers, the basement membranes of the kidneys are incapable of filtering waste products from the blood and facilitating normal urine production, thereby resulting in the release of blood and protein into the urine. The abnormalities of type IV collagen in kidney basement membranes cause gradual scarring of the kidneys, eventually leading to end-stage renal disease (ESRD). Progression of the disease leads to basement membrane thickening and gives a “basket-weave” appearance from splitting of the glomerular basement membrane (GBM), specifically the lamina densa layer. The accumulation of extracellular matrix in the GBM and the mesangium as a function of renal disease progression is a feature shared by a variety of glomerular diseases including Alport Syndrome.
Patients with Alport Syndrome frequently develop sensorineural hearing loss/deafness, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue of the retina. These eye abnormalities seldom lead to vision loss. Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport Syndrome than in affected females.
As there is no known cure for the condition, treatments are mostly geared towards providing symptomatic relief. Proteinuria is often treated with ACE inhibitors. Once kidney failure has developed, patients attempt to manage their condition with dialysis or surgery.